Current opinion in rheumatology最新文献

Purpose of review: Systemic lupus erythematosus (SLE) is a severe autoimmune/inflammatory disease. Patients with juvenile disease-onset and those of non-European ancestry are most severely affected. While the exact pathophysiology remains unknown, common and rare gene variants in the context of environmental exposure and epigenetic alterations are involved. This manuscript summarizes the current understanding of genetic and epigenetic contributors to SLE risk, manifestations and outcomes.

Recent findings: Though SLE is a mechanistically complex disease, we are beginning to understand the impact of rare and common gene variants on disease expression and associated outcomes. Recent trans -ancestral and multigenerational studies suggest that differential genetic and environmental impacts shape phenotypic variability between age-groups and ancestries. High genetic burden associates with young age at disease-onset, organ involvement, and severity. Additional epigenetic impact contributes to disease-onset and severity, including SLE-phenotypes caused by rare single gene variants. Studies aiming to identify predictors of organ involvement and disease outcomes promise future patient stratification towards individualized treatment and care.

Summary: An improved understanding of genetic variation and epigenetic marks explain phenotypic differences between age-groups and ancestries, promising their future exploitation for diagnostic, prognostic and therapeutic considerations.

Purpose of review: Updates from large, observational cohorts and new statistical techniques have resulted in new data on the epidemiology of systemic sclerosis (SSc). This scoping review uses data from 2018 to 2024 to describe the current understanding of the epidemiology of SSc and several of its organ- manifestations.

Recent findings: Our review identified new estimates for the global incidence and prevalence of SSc (1.4-8.6 per 100 000 person-years and 17.6-18.9 per 100 000 individuals, respectively). Mortality rates remain high, though mortality at younger ages has decreased. interstitial lung disease and pulmonary arterial hypertension remain the most common causes of death for patients with SSc. Literature on gastrointestinal (GI) manifestations of SSc was scarce, and we identified significant heterogeneity in results. Furthermore, data on the epidemiology of racial, ethnic and sex-based disparities was lacking.

Summary: New techniques for the evaluation of the epidemiology of SSc highlight the high morbidity and mortality of SSc, and a growing prevalence rate compared with prior eras. Further research is needed to address notable heterogeneity in the reporting of epidemiological data and understudied disease manifestations, including GI disease and health disparities in disease outcomes.

Purpose of review: Psoriatic arthritis is an immune-mediated disease that primarily affects the skin and joints. It falls under the umbrella term of rheumatic diseases, which describes a group of closely related yet distinct disorders with many common underlying molecular pathways. Despite the distinct clinical manifestation of each disorder, the shared therapeutic strategies attest to the commonality of cellular and molecular underpinnings. Herein we provide a concise yet comprehensive overview of the interleukin (IL)-23/IL-17 axis and its involvement in mechanistic pathways leading to the pathogenesis of this dual skin and joint clinical manifestation which is characteristic of psoriatic arthritis and other rheumatic diseases.

Recent findings: The interconnection between activated innate immune cells and adaptive immunity has transformed current thinking to include other organs such as the bone marrow as potential tissue of disease origin. A plethora of animal models and genetic studies converge on the critical role of IL-23/IL-17 axis, and highlight the importance of myeloid cell activation as common pathways between autoinflammatory and autoimmune diseases and chronic inflammation. These findings underscore the intricate immune mechanisms involved in inflammatory arthritis and highlight molecular mechanisms in disease pathogenesis.

Summary: These insights pave the way for the development of novel diagnostic and therapeutic strategies, with a focus on translating these findings into improved clinical practice.

Purpose of review: This review aims to synthesize recent developments in the epidemiology of idiopathic inflammatory myopathies (IIMs), focusing on incidence, prevalence, disease classification, and clinical outcomes.

Recent findings: IIM is a rare group of autoimmune diseases characterized by muscle weakness and systemic involvement, with incidence rates ranging from 0.2 to 2 cases per 100 000 person-years. The role of myositis-specific autoantibodies (MSAs) in stratifying disease risk and prognosis is increasingly recognized, such as in anti-MDA5 positive DM, which is associated with a high risk of rapidly progressive interstitial lung disease. Furthermore, patients with IIM exhibit elevated risks of comorbidities, including cardiovascular disease and malignancy.

Summary: IIM diseases are complex disorders with significant health impacts, necessitating enhanced awareness and research. Improved classification and understanding of MSAs are crucial for earlier diagnosis and tailored therapeutic strategies. Continued epidemiological research is essential to elucidate underlying mechanisms and inform future interventions, ultimately aiming to enhance the quality of life and clinical outcomes for affected patients.

Purpose of review: Aberrant autoreactive innate and adaptive immune responses cause systemic autoimmune diseases. Autoimmunity has been linked to abnormal metabolic states, and immunometabolism has emerged as a critical field in understanding the pathogenesis of rheumatic diseases. We aimed to explore the latest research on metabolic reprogramming in various immune cell types, including T cells, B cells, neutrophils, dendritic cells, monocytes, and macrophages, in the context of rheumatic diseases.

Recent findings: Each immune cell utilizes preferred metabolic pathways, and the cell activation dramatically modifies metabolic status. The inhibition of these pathways alters cell survival, differentiation, proliferation, and cytokine production - all of which contribute to rheumatic disease progression.

Summary: Targeting metabolic pathways or introducing anti-inflammatory metabolites, such as itaconate, could be novel therapeutic strategies for rheumatic diseases. Further research should focus on strategies for translating basic research findings to bedside applications.

Purpose of review: Ongoing research contributes to our understanding of the epidemiology of vasculitis and its outcomes across the globe. This review aims to summarize important research studies published on this topic in the last 18 months.

Recent findings: The implementation of rapid referral systems and use of large vessel imaging have improved the diagnosis of giant cell arteritis. A population-based study in immunoglobulin G4-related disease provides incidence and prevalence estimates for the United States for the first time. Recently published data supported viral infectious triggers for Kawasaki disease and immunoglobulin A vasculitis. Population studies in antineutrophil cytoplasmic antibody associated vasculitis report an increase in the incidence of eosinophilic granulomatosis with polyangiitis and have provided further insights into the burden of cardiovascular disease in these patients. Data on Behçet's disease continues to show increased all-cause mortality and need for better treatment strategies.

Summary: Recent literature highlights the heterogeneity of the epidemiology of vasculitis in different parts of the world as well as associated outcomes, comorbidities, and potential triggers. Thought new classification criteria are being employed in some forms of vasculitis, standardization of case identification remains an unmet need in multiple other forms of vasculitis.

Purpose of review: This review provides an update on the rapidly growing field of engineered cellular therapies for autoimmune disorders, primarily focusing on clinical experience and correlative studies with chimeric antigen receptor (CAR) T-cells.

Recent findings: To date, two case series describing treatment with CAR T-cell therapy for systemic lupus erythematosus (SLE) suggest that drug-free remission can be sustained in patients with previously treatment-refractory disease. The outcomes of these studies are similar, despite the use of different CAR constructs and lymphodepletion regimens. Although it is not yet clear whether the patients described have truly been cured, the majority of remissions have remained durable up to last follow-up at 1-2 years from treatment. Meanwhile, mechanistic studies are providing a window into how transient B-cell depletion mediates lasting benefit. With the encouraging data in SLE, CAR T-cells and other novel B-cell-depleting agents (e.g. bispecific T-cell engagers) are now being evaluated as treatment for other autoimmune conditions, with the goal of durable response.

Summary: Recent reports highlight cellular therapies as a promising strategy for patients with treatment-refractory autoimmune conditions; however, there is still limited experience, and better insight into this therapeutic approach is expected to emerge rapidly.

Purpose of review: Systemic vasculitides are characterized by inflammation of blood vessels. Their classification is based on the size of the blood vessels involved - large, medium, or small. Vasculitis early diagnosis and reliable monitoring are crucial to establish a treatment plan and prevent serious complications. Based on these considerations and depending on the location of the affected vessels, the importance of imaging modalities including ultrasonography (US), magnetic resonance Imaging (MRI), magnetic resonance angiography (MRA), computed tomography (CT), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy- d -glucose positron emission tomography/computed tomography (FDG-PET/CT) has progressively increased. In addition to physical exam and laboratory data, these imaging tools offer complementary information about vascular changes occurring in vasculitis.This review summarizes the different imaging modalities being utilized to diagnose and monitor vasculitis.

Recent findings: The most recent update for the use of imaging in vasculitis is referenced in the 2023 European Alliance of Associations for Rheumatology (EULAR) recommendations and the American College of Rheumatology (ACR) guidelines in 2021. Recent advances in PET imaging in large vessel vasculitis include improved technological imaging acquisition and the use of novel radiotracers for cellular and immune targets. FDG-PET has now been demonstrated to have high sensitivity and specificity to detect temporal arteritis.

Summary: Imaging plays a significant role in the evaluation of vasculitis and continues to gain importance in the diagnosis and monitoring of disease activity. Differences exist between the ACR guidelines, which advocates for temporal artery biopsy, and the EULAR guidelines, which favors imaging modalities for the initial evaluation and diagnosis of large vessel vasculitis (LVV). Prerequisites for appropriate clinical management utilizing imaging in patients with vasculitis are the availability and access to skilled clinicians to interpret the images and the cost of these techniques not being prohibitive.

Purpose of review: To review recent advances in our understanding of the epidemiology, pathophysiology, and management of inclusion body myositis (IBM).

Recent findings: Recent epidemiologic studies have highlighted the morbidity and mortality associated with IBM, including the impact of dysphagia. Multiomic analyses of IBM tissues have identified new pathogenic pathways and biomarkers for use in clinical trials. New diagnostic criteria and outcome measures have been proposed to improve clinical trial design. Ongoing clinical trials are targeting T cells and autophagy.

Summary: Improvements in our understanding of IBM pathogenesis are identifying new pathways and biomarkers that need validation in larger cohorts. Exercise remains the primary therapeutic modality available, and new treatment targets are needed.

Purpose of review: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by diffuse organ fibrosis and vasculopathy. Aberrant aging has been increasingly implicated in fibrotic diseases of the lung and other organs. The aim of this review is to summarize the established mechanisms of aging and how they may contribute to the pathogenesis of SSc.

Recent findings: Shortened telomeres are present in SSc patients with interstitial lung disease (SSc-ILD) and associate with disease severity and mortality. Although the cause of telomere length shortening is unknown, immune mechanisms may be at play. Senescent cells accumulate in affected organs of SSc patients and contribute to a pathologic cellular phenotype that can be profibrotic and inflammatory. In addition to identifying patients with a more severe phenotype, biomarkers of aging may help identify patients who have worse outcomes with immunosuppression.

Summary: Aging mechanisms, including telomere dysfunction and cellular senescence, likely contribute to the progressive fibrosis, vasculopathy, and immune dysfunction of SSc. Further work is needed to understand whether aberrant aging is an initiator or perpetuator of disease, and whether this is cell or organ specific. A better understanding of the role aging mechanisms play in SSc will contribute to our understanding of the underlying pathobiology and may also influence management of patients exhibiting the aging phenotype.